Predicting Prostate Cancer Risk Through Incorporation Of Prostate Cancer Gene 3

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 02 Oct 2008 - 1:00 PDT

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UroToday.com - Prostate cancer gene 3 is a promising new prostate cancer (CaP) biomarker as it is over-expressed in CaP tissue compared to normal prostate tissue. As such, Dr. Donna P. Ankerst and colleagues hypothesized that its inclusion in the Prostate Cancer Prevention Trial (PCPT) risk calculator may augment its predictive capabilities. Their research report appears in the October 2008 issue of the Journal of Urology.

Specimens for the analysis were collected from 521 patients at four North American centers - along with data on PCA3, PSA, DRE, age, race, and history of prostate biopsy. In addition, a cohort from Europe comprised of 443 patients at high risk for CaP, was evaluated for external validation of posterior risks.

A noted difference between the 521 men in the PCA3 group and the 5,519 men in the PCPT placebo group used to derive the PCPT risk calculator is that the PCPT cohort was a screened population. Only 11.7% of the PCPT placebo group had undergone a prior biopsy compared to 49.5% of the PCA3 group. Only 21.2% of CaP was high grade in the group of PCPT men, compared to 42.7% in the PCA3 cohort. This demonstrates that the PCA3 cohort was at a much greater risk for CaP and high-grade disease.

A "likelihood ratio" (LR) which expresses how much more likely a given PCA3 value is for cases vs. controls was used. A LR >1 means the PCA3 value is more often seen in cases while an LR <1 means the PCA3 value is more often seen in controls. LRs were <1 for all risk groups at PCA3 values <25, suggesting that PCA3 values less than this cutoff were less common in CaP cases vs. controls. PCA3 values >25 were more common in cases vs. controls, but the degree depended on age, PSA and DRE result. For example, a 65-year old patient with PSA at the commonly used cutoff of 2.5ng/ml and a normal DRE, a PCA3 value of 150 was 3 times more likely to be seen in cancer cases compared to controls. The increase in LR value for fixed PSA levels confirmed that PCA3 gave independent discriminatory power to PSA for CaP detection.

The data from the European patient cohort of 443 men was then applied to the calculator. The AUC of posterior risks was 0.696 and did not significantly differ statistically from the AUC of PCA3. Posterior risks, which combine PCA3 with the other risk factors in the PCPT calculator including PSA, did significantly improve on PSA and PCPT prior risks in the validated cohort. There was no statistical difference between the AUC of PCA3 and the AUC of PSA or PCPT prior risks in the validation cohort.

Ankerst DP, Groskopf J, Day JR, Blase A, Rittenhouse H, Pollock BH, Tangen C, Parekh D, Leach RJ, Thompson I
J Urol. 2008 Oct;180(4):1303-8
doi:10.1016/j.juro.2008.06.038

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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